撰文丨王聪 2025 年 11 月 25 日， 遵义医科大学第二附属医院 马虎 教授、 周建国 副主任医师作为共同通讯作者，在 Therapeutic Advances in Medical Oncology 期刊发 表了题为： CircRNA signature predicts immunotherapy response in advanced non-small cell lung cancer 的研究论文。 该研究系统性分析了两项 非小细胞肺癌 （NSCLC） 临床研究中的 circRNA 表达谱，识别出差异表达的 circRNA，进而 确定了一个由 11 个 circRNA 组成的 circRNA 特征谱—— circRNA-Sig ， 可用于预测晚期 非小细胞肺癌 （NSCLC） 对免疫治疗的响应，有望为肺癌的临床治疗提供指导。 编辑丨王多鱼 排版丨水成文 扫描 文末二维码 ，获取 生物世界 专属投稿折扣 肺癌 是全世界范围内最常见的恶性肿瘤，也是癌症相关死亡的首要原因，其中 非小细胞肺癌 （NSCLC） 占肺癌病例总数的 85%以上。尽管临床管理方面有所 进步，但非小细胞肺癌患者的 5 年总生 ...

Core Viewpoint - The in vivo CAR-T field has rapidly evolved over three years, marked by significant acquisitions and clinical advancements, culminating in major deals such as AbbVie’s $2.1 billion acquisition of Capstan Therapeutics and BMS’s $1.5 billion acquisition of Orbital Therapeutics [3][4]. Group 1: Acquisitions and Market Activity - AbbVie announced the acquisition of Capstan Therapeutics for $2.1 billion in cash, highlighting the growing interest in in vivo CAR-T therapies [3]. - BMS acquired Orbital Therapeutics for $1.5 billion, expanding its portfolio into the in vivo CAR-T cell therapy space [4]. - These acquisitions reflect a broader trend of increasing investment and collaboration in the CAR-T sector, indicating a robust market outlook [3][4]. Group 2: Technological Advancements - BMS's acquisition of Orbital enhances its cell therapy research platform, focusing on a potential best-in-class therapy aimed at autoimmune diseases [6]. - The therapy OTX-201, developed by Orbital, is in the pre-IND research stage and is expected to enter clinical trials in the first half of 2026 [6]. - OTX-201 utilizes optimized circular RNA (circRNA) to generate CAR-T cells in vivo, targeting CD19 to treat B-cell driven autoimmune diseases [7]. Group 3: Research and Development Focus - Orbital Therapeutics aims to develop next-generation RNA drugs that reprogram cells to treat diseases at their source, offering a simpler and safer alternative to current CAR-T therapies [10]. - The company’s platform integrates circRNA, linear RNA, targeted delivery systems, and AI-driven design to create durable and programmable therapies [10]. - In addition to autoimmune diseases, Orbital is also exploring in vivo CAR-T therapies for cancer and developing next-generation mRNA vaccines [12].

Core Insights - The article discusses the role of circular RNA (circRNA) in gene expression regulation, highlighting its importance in various biological processes and diseases, particularly cancer [2][8]. Group 1: CircRNA Mechanism and Function - Pre-mRNA reverse splicing leads to the production of circRNA, which shares nearly identical sequences with linear RNA but differs at the back-splicing junction (BSJ) [2]. - CircRNA plays significant roles in gene expression regulation, including transcription modulation, mRNA splicing interference, acting as "sponges" for miRNA or proteins, influencing translation, and even being translated into peptides [2]. - High-expression circRNA has been linked to maintaining quiescent hematopoietic stem cells, regulating cell growth and cancer progression, affecting brain function and neuronal development, and modulating innate immune responses [2]. Group 2: Research Findings on circMAN1A2 - A study published by Fudan University identified a circRNA, circMAN1A2(2,3,4,5), that is highly expressed in tumors and regulates colorectal cancer (CRC) development through RNA-RNA interactions [3][5]. - The research team analyzed the variable circularization (AC) patterns across multiple cell lines and CRC tissues, identifying the primary expressed circRNA at each AC gene locus [5]. - CircMAN1A2(2,3,4,5) enhances the stability of CENPB mRNA by interacting with its 3' untranslated region (3' UTR), and inhibiting this interaction can suppress CRC progression [7][8].